The aim of this renewal project is to apply detailed information on morphologically defined G1 phase cells and their cycling counterparts, acquired during studies reported in this application. Planned studies will be conducted in vivo on transplantable lines of murine mammary carcinomas and sarcomas, and on lines of human mammary carcinomas propagated in athymic-nude mice. Studies will be concerned with several problems: 1) The capacity of G1 phase-confined cells to recover from sublethal or potentially lethal radiation damage; 2) comparison of both types of repair in vivo; 3) exploration of a possibility that repair of radiation damage in some instances might be an artifact caused by dispersion procedures of tested tumor cells; 4) relationship between hypoxic cells and G1 phase-confined or proliferating cells; 5) kinetics and clonogenic potential of the "fast" and "slow" components of G1 phase-confined cells in untreated as well as in irradiated tumors; 6) automatization of nucleolar screening in tumor cells; and 7) application of diffusion chamber-semisolid medium technique to human carcinomas. Since these experiments will be performed on mouse tumor systems as well as on human mammary carcinomas, the clinical implication is inherent. The overall goals of the proposed research are: a) To extend the current knowledge of G1 phase-confined cells in experimental as well as in human tumors under in vivo conditions, b) to develop an in vivo experimental testing and screening system applicable to human cancers, and c) to apply this system to further exploration of combination therapy.